The principal objectives of this project are: 1) to establish the covalent structure of various genetically distinct types of collagens present in normal human aorta, identifying in particular the specific chemical features involved in the collagen-platelet interaction, 2) to extend these studies to examination for possible alterations in the collagen structure in arteriosclerosis, specifically in terms of the reactive chemical groups involved in interaction with platelet membranes, and 3) to investigate the biochemical events that follow the contact of platelet membranes with collagen and its fragments, which may bear on the mechanism of collagen-induced platelet aggregation. The particular parameters of the collagen structure to be examined will include amino acid and carbohydrate composition, the degree of hydroxylation of prolyl and lysyl residues and the nature of individual CNBr peptides of the isolated collagens and alpha chains of distinct genetic types. We will need to complete the chemical characterization and to determine the interacting properties with platelets of not only the better known types I and III collagens, but also the more recently discovered "unusual" collagens, i.e. type IV, A and B collagens. Where abnormalities are found in any of the above parameters in diseased aorta as compared to normal, they will be investigated further and pinpointed if possible to the specific amino acid sequence. Special attention will be focused on any alterations in the relative distribution of type I versus type III collagen, and type IV, A and B collagen chains in diseased aorta. Mechanisms of collagen-induced platelet aggregation will be approached by attempts to isolate, purify, and characterize the specific platelet membrane receptor protein(s) which we have previously described and the platelet proteins which become endogenously ohosphorylated when exposed to collagen or active collagen fragments.